Current Molecular Medicine - Volume 21, Issue 4, 2021

Nearly 15% of couples experience infertility as a universal health issue. About 50% of infertility cases have been known to be associated with the male partner . Oxidative stress (OS) represents an imbalance in the level of reactive oxygen species (ROS) and anti-oxidants. In fact, OS has been considered as one of the popular pathologies reported in about 50% of all infertile males. Therefore, the increased level of ROS may result in infertility via DNA damages or lipid peroxidation (LPO) as well as the inactivation of enzymes and oxidation of protiens in spermatozoa. Basically, OS results from lifestyle variables. As the absence of antioxidants and the respective deficiencies in the semen cause OS, variations in the lifestyle and anti-oxidant regimes may be advantageous to treatment strategies for resolving such an issue. Actually, anti-oxidants like vitamins E and C, glutathione, coenzyme-Q10, carnitines, selenium, Nacetylcysteine, carotenoids, zinc, and pentoxifylline decline the OS-induced sperm damages. Therefore, the present review overviews the oxidative biochemistry associated with sperm health and identifies which men would be most at risk of oxidative infertility. Hence, the review would show the techniques provided to diagnose OS and diverse therapeutic options.

Human microbiota and immune system are strictly connected to each other. Several studies demonstrated that normal skin and/or gut floral alterations may have negative consequences on disease pathogenesis. Indeed, a strong association between skin and gut microbiota alterations and autoimmune diseases was found. Moreover, a significant interplay between microbiome and miRNAs expression was noticed among several conditions. The aim of this review article is to shed new light on some of the commonest skin disorders such as psoriasis, atopic dermatitis, allergic contact dermatitis, with special regard to epigenetic pathogenetic mechanisms such as miRNAs expression and skin and gut microbiome alterations. Indeed, evidence is still lacking regarding these two factors and their possible interactions. We believe their implications may be crucial for screening, early diagnosis and also therapeutic strategies; therefore, this field could represent a promising challenge for further studies.

The “exterior-interior relationship between the lung and the large intestine” is a basic theory in Traditional Chinese Medicine (TCM), which has been confirmed by mounting evidence, and the lung-intestinal axis can be seen as an extension of this theory. Circular RNAs (circRNAs) are a kind of conserved and structurally stable noncoding RNAs, which have been found to be differentially expressed and associated with the development of cancer in malignant tumors. Many studies have found that circRNAs play an important role in lung and intestinal cancers. This review focuses on circRNAs and reveals that there are common circRNAs that are both highly or poorly expressed in lung-intestinal axis cancers and most of them regulate the proliferation, migration, and invasion of cancer cells by sponging miRNAs. These results not only provide new evidence and research ideas for the “exterior-interior relationship between the lung and the large intestine”, but also suggest that circRNAs can be new potential therapeutic targets for the future drug research of lung-intestinal axis diseases.

Aging is a complex multifactorial process that, although universal, is not fully understood. It is known that the impact of aging on health is influenced by multiple factors, such as sex, race, income, and education, and that age-related diseases are strongly associated with the way people get old. The knowledge of biological aging and its comparison to the chronological age is a paramount contributor to predict the metabolic decline and the onset of age-related diseases. As aging processes observed in the whole human organism are somehow the reflection of what happens in each cell type, it is possible to study the aging process using cell lines, such as fibroblasts. Metabolomics analysis of cell lines, namely fibroblasts, gives inputs to personalized or integrative medicine; in fact, cell metabolomics is an emerging field that addresses fundamental biological and metabolic questions using modern "omic" techniques as FTIR, NMR or MS. This paper revises the relevance of using fibroblasts as cell models to study the metabolome of aging.

Diabetes is a chronic disease characterized by marked alterations in the metabolism of glucose and by high concentrations of glucose in the blood due to a decreased insulin production or resistance to the action of this hormone in peripheral tissues. The International Diabetes Federation estimates a global incidence of diabetes of about 10% in the adult population (20 - 79 years old), some 430 million cases reported worldwide in 2018. It is well documented that people with diabetes have a higher susceptibility to infectious diseases and therefore show higher morbidity and mortality compared to the non-diabetic population. Given that the innate immune response plays a fundamental role in protecting against invading pathogens through a myriad of humoral and cellular mechanisms, the present work makes a comprehensive review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as well as a brief description of the molecular events leading or associated to such conditions. We show that in these patients a compromised innate immune response increases susceptibility to infections.

Prostate cancer (PC) is known as the most frequent cancer among men in the world. Androgen Deprivation Therapy (ADT) is one of the initial treatment approaches in the PC therapy and various drugs can be used in routine Hormonal therapy for PC therapy. Nevertheless, PC cells can survive and continue their growth via different mechanisms which lead to their resistance to common treatments i.e., Enzalutamide. olutamide (ODM-201) is a second-generation androgen receptor (AR) inhibitor with a new chemical structure and has a high affinity to the AR. Darolutamide does not cross the blood-brain barrier and for this reason, reduces the possibility of seizures. Darolutamide can also inhibit the transcriptional activity of several AR mutant variants (F877L, F877L/T878A, and H875Y/T878A), which are Enzalutamide resistant. In this review, we reviewed the results of different studies: in vitro, animal model and phase 1, 2 and 3 clinical trials (ARADES, ARAFOR and ARAMIS). We shall discuss worldwide phase 2 and 3 clinical trials (ARASENS and ODENZA) that are in progress, in order to demonstrate the advantages of Darolutamide consumption in different groups of patients. Darolutamide has shown high potential in inhibiting the growth of MR49F (Enzalutamide resistant PC cells) and VCaP (Castration-resistant PC cells) cell lines and transcriptional activities of AR. Fewer doses of Darolutamide are needed compared to Enzalutamide. The drug had significant anti-tumor activity and no effect on serum testosterone levels in animal models. Darolutamide demonstrates its safety and efficacy in different studies and was well tolerated nearly in all of the patients.

Annexin, a calcium-dependent phospholipid-binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “cross-talk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.